The objective of this proposal is to study the role of cell and membrane lipid composition on hyperthermic sensitivity. In preliminary experiments we have observed that experimental alteration of the fatty acid composition of an experimental tumor (L1210 lymphoblastic leukemia) results in a marked change in its sensitivity to heating. In different types of experiments conducted on cells grown in vitro, we will explore the mechanism by which lipid alterations affect heat sensitivity. We will search for associated changes in specific lipids, fluidity of subcellular fractions, cell cycle and lysosomal enzyme activation. We will also examine for interaction of lipid alteration with membrane active drugs which have a fluidizing effect (local anesthetic, Procaine Hydrochloride), and the cholesterol repletion/depletion on heat sensitivity. Furthermore, we will explore development of thermotolerance as a function of membrane lipid composition. In other experiments we will alter the lipid composition in vitro using diets to compare with in vitro alteration. Finally, we will examine the affect of cell lipid alteration produced by diet on the thermosensitivity of a murine solid tumor in vivo. Our long term objective is to develop a system by which special diets and heat can be utilized in the combined modality therapy of human tumors.